1. Jack DeRuiter, PhD Dept of Pharmacal Sciences April, 2000
RENAL DISEASE: Overview of Kidney Structure and Function Pathophysiology of Disease: Chapter 16 ( )
Jack DeRuiter, PhD
Dept of Pharmacal Sciences
April, 2000

2. Introduction (page 382) Renal Disease: General Characteristics:
Early Renal Disease: Abnormal urine volume and/or composition (electrolyes, proteins, cells)
Advanced: Edema, electrolyte abnormalities, anemia, etc.
Rate of Progression: Disease-dependent
Disease Course: Transient-fatal: Disease-dependent
Pain: Variable, depending on nature of disease
Renal Disease prominent in:
Diabetes Mellitus
Hypertension
Autoimmune disorders (SLE)

3. KIDNEY STRUCTURE AND FUNCTION
GROSS ANATOMY OF THE KIDNEY: (Page 382):
Location: Retroperitoneal
Blood flow: Renal Artery and Renal Vein
Flow from cortex to medulla
Medulla has relatively low blood flow and high metabolism; thus particularly susceptible to ischemic injury
Cardiac Output: 25%
Function:
Filter wastes from blood
Regulate electrolytes and intravascular volume
Modulation of other hormones/regulators
Anatomic/Functional Unit: Nephron

4. Anatomical Location and Gross Structure

5. Kidney: Blood Supply/Ureter

6. Kidney: Cross-Section

7. THE NEPHRON (pages 382, 384) Glomerulus Renal Tubule
Afferent and Efferent arteriole with intervening capillary tuft
Blood filtration site
Renal Tubule
Proximal Convoluted Tubule
Loop of Henle: Consists of descending, thin and thick ascending limbs
Distal Convoluted tubule
Collecting Ducts

8. NEPHRON: Overview 1: Interlobular artery 2: Interlobular Vein
3: Glomerulus/Bowman’s Capsule
4. Distal Tubule
5. Proximal Tubule
6: Loop of Henle
7: Collecting Duct

9. Cortical and Medullary Nephrons
Cortical nephrons: 85%
-peritubular capillaries encirling all nephron sections
Juxtamedullary nephrons: 15%
-some peritubular capillaries and vascular loops (vasa recta) which surround loop of Henle which descend into medulla

10. Glomerulus Structure Summary (pages 382-385)
Afferent and Efferent Arterioles
Juxtaglomerular apparatus
Capillary bed:
Endothelial Cells: Fenestrated/negatively charged
Epithelial Cells (“Podocytes”)
Basement Membrane
Mesangium: Intrinsic glomerular cells and macrophages

11. Glomerulus and Glomerular Capillary

12. Nephron: The Glomerulus (pages 382-384)

13. Glomerular Filtration (page 385)
Rate (GFR): 120 mL/min (normal)
Substances “Filtered”:
water, electrolytes (Na, K, etc.), sugars (glucose), nitrogenous waste (urea, creatinine)
Substances “Excluded”:
Substances of size > 70 kDa
Plasma protein bound substances

14. Tubular Resorption (page 385)
Proximal Tubules: GF: mL/min
Reabsorption of Na (55%), Cl, phosphate, amino acids, glucose and bicarbonate (85%). Secretion of proton (CA)
Loop of Henle: (30 mL/min)
Na/K/2Cl Cotransporter (25% Na reabsorbed)
Water impermeable: Hypertonic medullary inst
Ca & Mg paracellular diffusion
Distal Tubules:
EDT: Na/Cl cotransporter; Ca/Na counter transport
LDT: Na Channels, K channels, H pump: Aldosterone reg.
Collecting Tubules: 5-10 mL/min
Water channels: Vasopressin regulated
Ureters: 1-2 mL/min (stored inbladder until voiding)

15. Summary of Tubular Resorptive Processes

16. Role of the Kidney: Overview
The kidney excretes wastes, maintains fluid and electrolyte homeostasis, and is capable of responding to physiologic needs and variation by generating either a concentrated or dilute urine:
Counter-current multiplier in the loop of Henle
Hypertonic medulary interstitium
Vassopressin and other hormones

17. Regulation of Renal Function (page 387)
Tubuloglomerular feedback
Medullary Vasoconstriction
Medullary Vasodilation
Inhibition of transport in the thick ascending limbs

18. Regulation of Renal Function (page 387)
Tubuloglomerular Feedback: Regulation of GFR in response to solute concentration in the distal tubule:
macula densa (PCT): Afferent arteriolar vasoconstriction in response to high tubular Na (Decr GFR)
Juxtaglomerular apparatus (Afferent): Renin release and angiotensin II formation with low perfusion pressure (Aldosterone secretion and Na and water retention)

19. Regulation of Renal Function (page 387)
Cortical Flow: Adequate to maintain GFR
Medullary Blood Flow and Oxygen demand:
Important for nephron cell survival and function (oxygen is required for ATP, used in trnasporters)
Too high: Disruption of osmolar gradient of counter-current exchange mechanism
Too low: hypoxic injury
Modulators: Table 16-2 (page 387)

20. Regulation of Renal Function (page 387)
Adaptive Changes:
Glomerular hyperfiltration (increased GFR per nephron) nephron loss. ( may progress to chronic renal failure).
Neural and Hormonal regulation: low perfusion results in afferent arteriolar vasodilation and efferent arteriolar vasconstriction
Alteration in Na systemic balance
Renal nerve (sympathetic)

21. The Kidney and Physiologic Regulation: Blood Pressure (pages 385-386)
Macula Densa and Na concentration
Juxtaglomerular Apparatus and Renin release and angiotensin II production
Direct vasoconstriction
Aldosterone Secretion: na and water rentention
Vasopressin and intravascular volume depletion: Enhanced water resorption at the collecting ducts
Morphologic: i.e. number of nephrons, etc.

22. The Kidney and Physiologic Regulation: Calcium Metabolism (page 386-387)
Formation of the active form of vitamin D required for Ca absorption from gut, etc.
Site of Parathyroid Hormone action: Ca retention and phosphate wasting (see earlier endocrine lectures)

23. The Kidney and Physiologic Regulation: Erythropoiesis (page 387)
Erythropoietin stimulates bone marrow production and maturation of RBCs.
Profound anemia in ESRD:
hematocrits 20-25%
Therapy: Erythropoietin administration